Diesel exhaust particles induced release of interleukin 6 and 8 by (primed) human bronchial epithelial cells (BEAS 2B) in vitro.
Several epidemiological studies have recently shown associations of increased premature mortality rates with ambient particulate air pollution. Diesel exhaust particles (DEP) may constitute an important part of (ultra)fine particulate air pollution in urban areas and may therefore contribute to its toxicity. Epithelial lining of the respiratory tract may be the first target of the toxic effects of DEP, that upon exposure may release pro-inflammatory mediators such as interleukin 6 and 8 (IL-6, IL-8), ultimately causing airway tissue damage and immune alterations. In this study the effects of in vitro DEP exposure (0.04-0.33 mg/mL) on IL-6, IL-8 production by a human bronchial epithelial cell line (BEAS-2B) were investigated. For comparison, the production of interleukins during exposure to silica and titanium oxide (TiO2) were also studied, representing relatively toxic and non-toxic particles, respectively. Scanning and transmission electron microscopy showed that the size of the DEP particles ranged between 25 to 35 nm and that DEP was phagocytized by BEAS-2B cells. An increase in IL-6 and IL-8 production (11- and 4-fold, respectively) was found after 24 or 48 h of exposure to DEP compared to the non-exposed cells. This increase was lower compared to silica (17- and 3.3-fold) and higher as compared to TiO2 which showed no increase for IL-6 and IL-8. To study the DEP effect on inflammation-primed cells, BEAS-2B cells were exposed to both tumor necrosis factor-alpha (TNF-alpha) and subsequently to DEP. Exposure to TNF-alpha caused a strong increase in IL-6 and IL-8 production. Additive effects on the IL-6 and IL-8 production by BEAS-2B cells were found after TNF-alpha priming and subsequently exposure to DEP, only at a low dose of DEP and TNF-alpha (0.05-0.2 ng/mL). In conclusion, BEAS-2B phagocytized DEP and produced an increased amount of IL-6 and IL-8. In TNF-alpha primed BEAS-2B cells, DEP increased interleukin production only at low concentrations of DEP and TNF-alpha. Whether this increased production of pro-inflammatory interleukins affects vulnerable balances in the immune system, such as T help-1 and T help-2 subsets ratios, resulting in an altered resistance to respiratory tract infections or altering the expression of respiratory allergy, is the subject of further studies.
Steerenberg
P A
PA
Laboratory for Pathology and Immunobiology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands. p.steerenberg@rivm.nl
Zonnenberg
J A
JA
Dormans
J A
JA
Joon
P N
PN
Wouters
I M
IM
van Bree
L
L
Scheepers
P T
PT
Van Loveren
H
H
D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism*; D002461:Cell Line, Transformed; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D012822:Silicon Dioxide / Q000633:toxicity; D014025:Titanium / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D001335:Vehicle Emissions / Q000633:toxicity*
D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D001335:Vehicle Emissions; C009495:titanium dioxide; D012822:Silicon Dioxide; D014025:Titanium; D007770:L-Lactate Dehydrogenase